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The exposure to cooking organic aerosols (COA) is closely related to people's daily lives. Despite extensive investigations into COA's model compounds like oleic acid, the intricacies of heterogeneous ozonolysis of real COA and the effects of ambient conditions like humidity remain elusive. In this work, the ozonolysis of COA proxies from heated peanut oil emissions was investigated using diffuse reflectance infrared Fourier transform (DRIFTS) spectroscopy, and proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS). We found that humidity hinders the reaction between ozone and CC double bonds due to the competitive adsorption of water and ozone on COA. Although visible light has little influence on the ozonolysis of COA in the absence of humidity, the ozonolytic CO production is significantly promoted by visible light in the presence of humidity. It may be attributed to the formation of water-derived reactive oxygen species (ROS, mainly HOâ¢) from the photosensitization of polycyclic aromatic hydrocarbons (PAHs) in COA. We also found that humidity can enhance the depolymerization of carboxylic acid dimers and hydrolysis of intrinsic acetals in the COA. Moreover, humidity promotes the release of VOCs during both the dark and light ozonolysis of COA. This work reveals the important roles of humidity-responsive and photo-responsive components in COA during its ozonolysis, and the change in VOC release may guide the control of human VOC exposure in indoor air.
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Objective: This study aimed to analyze the effect of modular nursing model for typical issues on enteral nutrition status, immune function, and quality of life in patients with colon cancer. Methods: The clinical data of 106 colorectal cancer patients who came to our hospital from January 2020 to January 2022 were retrospectively analyzed. The patients were randomized into the control and observation group based on the different nursing models, with 53 cases in each group. The patients in the control group received a simple enteral nutrition nursing model, while these in the observation group were administrated with a modular nursing model for typical issues on the basis of the control group. The differences in enteral nutrition status, immune function, and quality of life indicators of patients before and after nursing were counted and compared between the two groups. Results: After the nursing, the contents of albumin, serum albumin, and transferrin were all elevated in both two groups compared with these before the nursing (P < 0.001), and these contents in observation group was markedly higher than these in the control group after the nursing (P < 0.001). The expressions of immune function indicators, including CD3+, CD4+, CD4+/CD8+, and SIgA of the two groups after the nursing, were much higher than these before the nursing (P < 0.05), while the contents of CD8+ and IgG were sharply decreased in comparison with these before the nursing (P < 0.05). The improvement of immune indicators in the observation group after the nursing was strongly better than that in the control (P < 0.01). The proportion of the total nursing satisfaction was significantly higher in the observation group than that in the control (P < 0.05). After the nursing, the life quality scores of two groups were both strongly elevated (P < 0.05), and the improvement of life quality scores were memorably better in the observation group after nursing than these in the control (P < 0.01). Conclusion: For patients undergoing radical colon cancer resection, modular nursing model for typical issues in the early postoperative period is not only safe, but also improves enteral nutrition, can better maintain immune function in the early postoperative period, improve nursing satisfaction, improve patient prognosis, and promote the improvement of the condition, which is worthy of popularization and application.
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To explore the effect of the temperature chain management scheme on inadvertent perioperative hypothermia (IPH) during robot-assisted radical resection of urological tumors. Fifty male patients who underwent elective robot-assisted radical prostatectomy (RARP) or robot-assisted radical cystectomy (RARC) surgery from February 2022 to March 2023 in a teaching hospital were enrolled and randomized to receive either intraoperative warming, including forced-air warming blanket and prewarming fluid (group C) or the temperature chain management involving an active warming bunch covering the whole perioperative period (group T). Comparing the core temperature, IPH rates, the incidence of shivering, recovery from anesthesia, and thermal between the two groups. Perioperative core temperature of group T was higher compared with group C (p < 0.05); IPH rates and the incidence of shivering in postanesthesia care unit (PACU) of group T were lower compared with group C (p < 0.05); group T scored higher in thermal comfort compared with group C after PACU 15 minutes, after PACU 30 minutes, and when leaving the PACU (p < 0.05); group T took shorter time on recovering from anesthesia (p < 0.05). Temperature chain management could reduce IPH and postoperative complications during RARP and RARC.
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Breast cancer has become the malignant disease with the highest morbidity and mortality among female cancer patients. The prognosis of metastatic breast cancer is very poor, and the therapeutic effects still need to be improved. The molecular mechanism of breast cancer has not been fully clarified. Bioinformatics analysis was used to find the differentially expressed gene that affects the occurrence and development of breast cancer. Furthermore, scratch assays, Transwell assays, immunofluorescence, and Western blotting were used to determine the biological behavior of breast cancer cells affected by DEP domain-containing protein 1B (DEPDC1B). The molecular mechanism was investigated by mass spectrometry analysis, coimmunoprecipitation, and ubiquitin assays. Here, we found that DEPDC1B was highly expressed in breast cancer cells and tissues and was associated with lower overall survival (OS) in patients. We found that DEPDC1B interference significantly inhibited tumor invasion and migration in vitro and tumor metastasis in vivo. Mechanistically, DEPDC1B was first shown to activate the wnt/ß-catenin signaling pathway as an oncogene in breast cancer cells. In addition, we also confirmed the interaction between DEPDC1B, ubiquitin-specific protease 5 (USP5), and ß-catenin. Then, we found that DEPDC1B mediates the deubiquitination of ß-catenin via USP5, which promotes cell invasion and migration. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be considered a potential therapeutic target for breast cancer.NEW & NOTEWORTHY By using bioinformatics analysis and the experimental techniques of cell biology and molecular biology, we found that DEP domain-containing protein 1B (DEPDC1B) can promote the invasion and migration of breast cancer cells and that DEPDC1B mediates the deubiquitination of ß-catenin by ubiquitin-specific protease 5 (USP5), thus activating the wnt/ß-catenin pathway. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be used as a potential therapeutic target for breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , beta Catenina/genética , Via de Sinalização Wnt , Proteases Específicas de Ubiquitina/genética , Proteínas Ativadoras de GTPase , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Small pulmonary nodules (<3 cm) can sometimes be unrecognizable and nonpalpable in video-assisted thoracoscopic surgery (VATS). Near-infrared fluorescence (NIF) VATS after indocyanine green (ICG) inhalation may effectively guide surgeons to locate the nodules. OBJECTIVE: This study aimed to investigate the safety, feasibility, and efficacy of ICG inhalation-based NIF imaging for guiding small pulmonary nodule resections. METHODS: Between February and May 2021, the first-stage, non-randomized trial enrolled 21 patients with different nodule depth, ICG inhalation doses, post-inhalation surgery times, and nodule types at a tertiary referral hospital. Between May 2021 and May 2022, the second-stage randomized trial enrolled 56 patients, who were randomly assigned to the fluorescence VATS (FLVATS) or the white-light VATS (WLVATS) group. The ratio of effective guidance and the time consumption for nodule localization were compared. RESULTS: The first-stage trial proved this new method is safe and feasible, and established a standardized protocol with optimized nodule depth (≤1 cm), ICG dose (0.20-0.25 mg/kg), and surgery window (50-90 min after ICG inhalation). In the second-stage trial, the FLVATS achieved 87.1% helpful nodule localization guidance, which was significantly higher than the WLVATS (59.1%, p < 0.05). The mean nodule locating time (standard deviation) was 1.8 [0.9] and 3.3 [2.3] min, respectively. Surgeons adopting FLVATS were significantly faster (p < 0.01), especially when locating small ground-glass opacities (1.3 [0.6] min vs. 7.0 [3.5] min, p < 0.05). Five of 31 nodules (16.1%) were only detectable by FLVATS, whereas both white light and palpation failed. CONCLUSIONS: This new method is safe and feasible for small pulmonary nodule resection. It significantly improves nodule localization rates with less time consumption, and hence is highly worthy for clinical promotion. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100047326.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Verde de Indocianina , Cirurgia Torácica Vídeoassistida/métodos , Neoplasias Pulmonares/cirurgia , Tomografia Computadorizada por Raios X/métodos , Pulmão , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgiaRESUMO
Cancer metastasis is a major cause of mortality from several tumors, including those of the breast, prostate, and the thyroid gland. Since bone tissue is one of the most common sites of metastasis, the treatment of bone metastases is crucial for the cure of cancer. Hence, disease models must be developed to understand the process of bone metastasis in order to devise therapies for it. Several translational models of different bone metastatic tumors have been developed, including animal models, cell line injection models, bone implant models, and patient-derived xenograft models. However, a compendium on different bone metastatic cancers is currently not available. Here, we have compiled several animal models derived from current experiments on bone metastasis, mostly involving breast and prostate cancer, to improve the development of preclinical models and promote the treatment of bone metastasis.
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Purpose: To examine clinical outcomes of a specialized modular prosthesis used to fill a bone deficiency following removal of femoral shaft metastases. Methods: Eighteen patients with femoral shaft metastases who underwent en bloc resection and implantation of a personalized modular prosthesis between December 2014 and December 2019 were retrospectively analyzed. Pain, limb function, and quality of life were evaluated using the visual analog scale (VAS), Musculoskeletal Tumor Society (MSTS) scale, International Society of Limb Salvage (ISOLS) scoring system, Karnofsky Performance Status (KPS) scale, and Nottingham Health Profile (NHP) scale. The Kaplan-Meier technique was used to analyze patient survival. Results: The operation duration was 90-150 min (mean, 115 min), and the osteotomy length was 9-16 cm (mean, 11.72 cm). The patients were followed for 12-62 months (mean, 25.28 months). The VAS and NHP ratings were lower at 3, 6, and 12 months after surgery than before surgery, while the MSTS, ISOLS, and KPS scores were higher after surgery than they had been before. These differences were statistically significant (P<0.05). The survival period was between 7 and 62 months (mean, 20.89 months), and the rates of survival at 1-year and 2-year were 72.22% and 27.78%, respectively. Except for two patients with aseptic prosthesis loosening during the follow-up period, there were no problems. Conclusion: En bloc excision and implantation of a personalized modular prosthesis can reduce pain and improve the ability of patients with femoral shaft metastases to perform daily activities, thereby improving their quality of life.
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There is no unified surgical plan for fibular proximal malignant tumours; therefore, the present study retrospectively analysed the medical records of 19 patients with primary malignant and invasive tumours in the proximal fibula and discussed the postoperative oncological results, complications and postoperative functions of limb salvage surgery. According to pathological classification, there were 10 osteosarcoma cases, 3 chondrosarcoma cases, 2 invasive giant cell osteosarcoma tumour cases, 1 epithelioid sarcoma case, 1 leiomyosarcoma case, 1 fibrosarcoma case and 1 lymphoma case. According to the Enneking instalment, IB stage was found in 2 cases, IIA in 2 cases and IIB in 15 cases. A total of 3 patients underwent Malawer I resection, and 16 patients underwent Malawer II resection. The follow-up period was 11-174 months, with an average of 76.58 months. Local recurrence occurred in three patients and distant metastasis in seven patients; 4 patients succumbed and 15 survived. After biceps femoris tendon reconstruction and lateral collateral ligament insertion, 18 patients had good knee stability. The Musculoskeletal Tumour Society scale ranged between 23 and 29 points, with an average of 27.26 points; the Lysholm Knee Score was 65-84 points, with an average of 83 points. After the resection of proximal fibula primary and invasive tumours, the biceps femoris tendon and lateral collateral ligament insertion point was reconstructed. The data show that this technique can effectively reconstruct stability and restore knee function.
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Fe(III) and carboxylic acids are common compositions in atmospheric microdroplet systems like clouds, fogs, and aerosols. Although photochemical processes of Fe(III)-carboxylate complexes have been extensively studied in bulk aqueous solution, relevant information on the dynamic microdroplet system, which may be largely different from the bulk phase, is rare. With the help of the custom-made ultrasonic-based dynamic microdroplet photochemical system, this study examines the photochemical process of Fe(III)-citric acid complexes in microdroplets for the first time. We find that when the degradation extent of citric acid is similar between the microdroplet system and the bulk solution, the significantly lower Fe(II) ratio is present in microdroplet samples due to the rapider reoxidation of photogenerated Fe(II). However, by replacing citric acid with benzoic acid, no much difference in the Fe(II) ratio between microdroplets and bulk solution is observed, which indicates distinct reoxidation pathways of Fe(II). Moreover, the presence of â¢OH scavenger, namely, methanol, greatly accelerates the reoxidation of photogenerated Fe(II) in both citric acid and benzoic acid situations. Further experiments reveal that the high availability of O2 and the citric acid- or methanol-derived carbon-centered radicals are responsible for the rapider reoxidation of Fe(II) in iron-citric acid microdroplets by prolonging the length of HO2â¢- and H2O2-involved radical reaction chains. The results in this study may provide a new understanding about iron-citric acid photochemistry in atmospheric liquid particles, which can further influence the photoactivity of particles and the formation of secondary organic aerosols.
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Ácido Cítrico , Ferro , Ferro/química , Ácido Cítrico/química , Peróxido de Hidrogênio/química , Fotoquímica , Metanol , Oxirredução , Ácidos Carboxílicos/química , Compostos Ferrosos , Aerossóis , Benzoatos , Compostos Férricos/químicaRESUMO
BACKGROUND: Osteosarcoma is a malignant bone tumor that usually affects adolescents aged 15-19 y. The DNA damage response (DDR) is significantly enhanced in osteosarcoma, impairing the effect of systemic chemotherapy. Targeting the DDR process was considered a feasible strategy benefitting osteosarcoma patients. However, the clinical application of DDR inhibitors is not impressive because of their side effects. Chinese herbal medicines with high anti-tumor effects and low toxicity in the human body have gradually gained attention. 2-Hydroxy-3-methylanthraquinone (HMA), a Chinese medicine monomer found in the extract of Oldenlandia diffusa, exerts significant inhibitory effects on various tumors. However, its anti-osteosarcoma effects and defined molecular mechanisms have not been reported. METHODS: After HMA treatment, the proliferation and metastasis capacity of osteosarcoma cells was detected by CCK-8, colony formation, transwell assays and Annexin V-fluorescein isothiocyanate/propidium iodide staining. RNA-sequence, plasmid infection, RNA interference, Western blotting and immunofluorescence assay were used to investigate the molecular mechanism and effects of HMA inhibiting osteosarcoma. Rescue assay and CHIP assay was used to further verified the relationship between MYC, CHK1 and RAD51. RESULTS: HMA regulate MYC to inhibit osteosarcoma proliferation and DNA damage repair through PI3K/AKT signaling pathway. The results of RNA-seq, IHC, Western boltting etc. showed relationship between MYC, CHK1 and RAD51. Rescue assay and CHIP assay further verified HMA can impair homologous recombination repair through the MYC-CHK1-RAD51 pathway. CONCLUSION: HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Adolescente , Reparo de DNA por Recombinação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Rad51 Recombinase/farmacologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
We report a clinical case of using indocyanine green inhalation to achieve intraoperative near-infrared fluorescence visualization of pulmonary ground-glass opacity in thoracoscopic wedge resection. The patient underwent thoracoscopic wedge resection under the real-time navigation of a near-infrared fluorescence imaging system with the indocyanine green inhalation performed 85 minutes before the surgery. The nebulized inhalation of indocyanine green (dose of 0.25 mg/kg) successfully guided surgeons to localize the small ground-glass opacity due to a filling defect of the fluorescence. The thoracoscopic near-infrared fluorescence navigation system delineated the tumor margin with high contrast and helped to minimize the damage to lung function.
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Verde de Indocianina , Neoplasias Pulmonares , Humanos , Fluorescência , Toracoscopia/métodos , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgiaRESUMO
Context: Lung cancer is one of the most common forms of cancer. Autophagy and apoptosis play an important role in the development of lung cancer. Researchers have found upregulation of GRP78 expression in cancer cells of various types. Objective: The study intended to explore the mechanism of G protein-coupled receptor 78(GPR78) in regulating autophagy and drug resistance in non-small cell lung cancer (NSCLC). Design: The research team performed a laboratory study. Setting: The study took place in the Department of Thoracic Surgery at Hainan General Hospital of the Hainan Affiliated Hospital of Hainan Medical University in Haikou, Hainan, China. Intervention: The research team cultured immortalized, normal, human bronchial epithelial cells C3 (HBEC3) lines and HBEC4 lines in a serum medium without keratinocytes and infected the expression of GPR78 in knockdown A549 cells using lentiviral agents. The team divided the cells into a control group and a shRNA-GPR78 group, the intervention group. The lentiviral silencing vector expressing shRNA targets human GPR78#1 and GPR78 #2aadam10. Outcome Measures: The research team analyzed the mRNA expression of GPR78 in the NSCLC cell lines H1975, H1299, and A549 and in HBEC3 and HBEC4 using a real time-polymerase chain reaction (RT-PCR) and measured the proliferation of A549 cells at 0h, 24h, 48h, 72h, and 96h using yellow tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The team also analyzed the migration and invasion ability of cells using wound healing and Transwell tests as well as measured the protein expression of the autophagy-related factors Beclin-1, microtubule-associated protein light chain 3-I/II (LC3-I/LC3-II), ubiquitin-binding protein p62 and c-Jun N-terminal kinase (JNK) using a Western blot test. The team also analyzed the protein expressions of caspase-9, caspase-3, and caspase-12 related to apoptosis using a Western blot. To detect the cell viability induced by cisplatin, the team used a Cell Counting Kit 8 (CCK-8) at the concentrations of 1µM, 3µM and 10µM. Results: The mRNA expression of GPR78 in the H1975, H1299, and A549 cell lines was significantly higher than that in the HBEC3 and HBEC4 cell lines (P < .05). At 48h, 72h, and 96h, the A549 cell proliferation in the shRNA-GPR78 group was significantly lower than that of the control group (P < .05). The cell migration and invasion of cells in the shRNA-GPR78 group was significantly lower than that in the control group (P < .05), and the cell viability of the shRNA-GPR78 group was significantly lower than that of control group (P < .05). The expression of Beclin-1 and JNK protein in shRNA-GPR78 group was significantly higher than that in the control group (P < .05), and the expression of LC3-I/LC3-II and p62 protein in shRNA-GPR78 group was significantly lower than that in the control group (P < .05). The protein expressions of caspase-9, caspase-3, and caspase-12 in the shRNA-GPR78 group were significantly higher than those of the control group (P < .05), and the protein activities of RhoA and Rac1 in the shRNA-GPR78 group were significantly lower than those in the control group (P < .05). Conclusion: NSCLC upregulated GPR78. The knockdown of GPR78 can attenuate the proliferation, migration, and invasion of NSCLC cells and increase the apoptosis and autophagy of NSCLC cells that cisplatin has induced. Therefore, targeting GPR78 may be a promising treatment strategy for NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Caspase 3/uso terapêutico , Caspase 9 , Proteína Beclina-1 , Caspase 12/uso terapêutico , Linhagem Celular Tumoral , Apoptose , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Proliferação de Células , Autofagia , Resistência a Medicamentos , RNA MensageiroRESUMO
Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.
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Neoplasias Ósseas , Osteossarcoma , Adolescente , Antígeno B7-H1/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Ácido Fólico , Humanos , Janus Quinase 2/metabolismo , Lipossomos/farmacologia , Lipossomos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Fator de Transcrição STAT3/metabolismoRESUMO
Cancer of unknown primary site (CUP) is a heterogeneous group of cancers whose tissue of origin remains unknown after detailed investigation by conventional clinical methods. The number of CUP accounts for roughly 3%-5% of all human malignancies. CUP patients are usually treated with broad-spectrum chemotherapy, which often leads to a poor prognosis. Recent studies suggest that the treatment targeting the primary lesion of CUP will significantly improve the prognosis of the patient. Therefore, it is urgent to develop an efficient method to accurately detect tissue of origin of CUP in clinical cancer research. In this work, we developed a novel framework that uses Extreme Gradient Boosting (XGBoost) to trace the primary site of CUP based on microarray-based gene expression data. First, we downloaded the microarray-based gene expression profiles of 59,385 genes for 57,08 samples from The Cancer Genome Atlas (TCGA) and 6,364 genes for 3,101 samples from the Gene Expression Omnibus (GEO). Both data were divided into training and independent testing data with a ratio of 4:1. Then, we obtained in the training data 200 and 290 genes from TCGA and the GEO datasets, respectively, to train XGBoost models for the identification of the primary site of CUP. The overall 5-fold cross-validation accuracies of our methods were 96.9% and 95.3% on TCGA and GEO training datasets, respectively. Meanwhile, the macro-precision for the independent dataset reached 96.75% and 98.8% on, respectively, TCGA and GEO. Experimental results demonstrated that the XGBoost framework not only can reduce the cost of clinical cancer traceability but also has high efficiency, which might be useful in clinical usage.
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Pyruvate kinase M2 (PKM2) plays an important role in the consumption of glucose and the production of lactic acid, the striking feature of cancer metabolism. The association of PKM2 with osteosarcoma (OS) has been reported but its role in OS has yet to be elucidated. To study this, PKM2bound RNAs in HeLa cells, a type of cancer cells widely used in the study of molecular function and mechanism, were obtained. Peak calling analysis revealed that PKM2 binds to long noncoding RNAs (lncRNAs), which are associated with cancer pathogenesis and development. Validation of the PKM2lncRNA interaction in the human OS cell line revealed that lncRNA colon cancer associated transcript1 (lncCCAT1) interacted with PKM2, which upregulated the phosphorylation of sterol regulatory elementbinding protein 2 (SREBP2). These factors promoted the Warburg effect, lipogenesis, and OS cell growth. PKM2 appears to be a key regulator in OS by binding to lncCCAT1. This further extends the biological functions of PKM2 in tumorigenesis and makes it a novel potential therapeutic for OS.
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Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Osteossarcoma/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Proteínas de Transporte/efeitos dos fármacos , Proteínas de Transporte/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Humanos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/genética , Osteossarcoma/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Hormônios Tireóideos/genética , Efeito Warburg em Oncologia/efeitos dos fármacos , Proteínas de Ligação a Hormônio da TireoideRESUMO
The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient's show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.
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BACKGROUND: Anal squamous cell carcinoma (ASCC) is the main subtype of anal cancer and has great heterogeneity in prognosis. We aimed to construct a nomogram for predicting their 1-, 3-, and 5-year overall survival (OS) rates. METHODS: Patients with ASCC, enrolled between January 1, 2010 and December 31, 2017, were identified from the SEER database. They were divided into a training group and a validation group in a ratio of 7:3. Univariate and multivariate Cox analyses were used to identify the prognostic factors for OS. Then a prognostic nomogram was established and validated by Harrell consistency index (C-index), area under the curve (AUC) of the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). RESULTS: We identified 761 patients in training group and 326 patients in validation group. Four prognostic factors including age, sex, AJCC stage, and radiotherapy were identified and integrated to construct a prognostic nomogram. The C-index and AUC values proved the model's effectiveness and calibration plots manifested its excellent discrimination. Furthermore, in comparison to the AJCC stage, the C-index, AUC, and DCA proved the nomogram to be of good predictive value. Finally, we constructed a risk stratification model for dividing patients into low-risk, medium-risk, and high-risk groups, and there were obvious differences in OS. CONCLUSIONS: A prognostic nomogram was firstly established for predicting the survival probability of ASCC patients and helping clinicians improve their risk management.
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Neoplasias do Ânus/mortalidade , Carcinoma de Células Escamosas/mortalidade , Nomogramas , Idoso , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , Área Sob a Curva , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Curva ROC , Programa de SEER , Taxa de SobrevidaRESUMO
Tumour-derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell-free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan-cancer patients of Chinese and explored effects of CH on liquid biopsies in real-world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K-Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty-eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision-making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real-world.